NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

Abstract

How neuronal proteomes self-organize is poorly understood because of their inherent molecular and cellular complexity. Here, focusing on mammalian synapses we use blue-native PAGE and ‘gene-tagging’ of GluN1 to report the first biochemical purification of endogenous

NMDA receptors (NMDARs) directly from adult mouse brain. We show that NMDARs partition between two discrete populations of receptor complexes and B1.5MDa supercomplexes.

We tested the assembly mechanism with six mouse mutants, which

indicates a tripartite requirement of GluN2B, PSD93 and PSD95 gate the incorporation of receptors into B1.5MDa supercomplexes, independent of either canonical PDZ-ligands or GluN2A. Supporting the essential role of GluN2B, quantitative gene-tagging revealed a fourfold molar excess of GluN2B over GluN2A in adult forebrain. NMDAR supercomplexes

are assembled late in postnatal development and triggered by synapse maturation involving epigenetic and activity-dependent mechanisms. Finally, screening the quaternary organization of 60 native proteins identified numerous discrete supercomplexes that populate the

mammalian synapse.

Metadata

Authors/Creators:	Frank, RAW https://orcid.org/0000-0001-9724-9547 Komiyama, NH Ryan, TJ Zhu, F O’Dell, TJ Grant, SGN
Copyright, Publisher and Additional Information:	© 2018, Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Dates:	Accepted: 4 March 2016 Published (online): 27 April 2016 Published: 27 April 2016
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	19 Sep 2018 11:42
Last Modified:	16 Sep 2020 15:30
Status:	Published
Publisher:	Nature Publishing Group
Identification Number:	https://doi.org/10.1038/ncomms11264

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NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

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